title: Neurophysiological and immunohistochemical studies of IgG anti-GM1 monoclonal antibody on neuromuscular transmission: effects in rat neuromuscular junctions.
abstract: Guillain-Barré syndrome, which is a variant of acute inflammatory neuropathy, is associated with anti-GM1 antibodies and causes ataxia. We investigated the effects of IgG anti-GM1 monoclonal antibody (IgG anti-GM1 mAb) on spontaneous muscle action potentials in a rat spinal cord-muscle co-culture system and the localization of IgG anti-GM1 mAb binding in the rat hemi-diaphragm. The frequency of spontaneous muscle action potentials in innervated muscle cells was acutely inhibited by IgG anti-GM1 mAb. When cultures were pretreated with GM2 synthase antisense oligodeoxynucleotide, IgG anti-GM1 mAb failed to inhibit spontaneous muscle action potentials, demonstrating the importance of the GM1 epitope in the action of IgG anti-GM1 mAb. Immunohistochemistry of rat hemi-diaphragm showed that IgG anti-GM1 mAb binding overlapped with neurofilament 200 (NF200) antibodies staining, but not α-bungarotoxin (α-BuTx) staining, demonstrating that IgG anti-GM1 mAb was localized at the presynaptic nerve terminal. IgG anti-GM1 mAb binding overlapped with syntaxin antibody and S-100 antibody in the nerve terminal. After collagenase treatment, IgG anti-GM1 mAb and NF200 antibodies did not show staining, but α-BuTx selectively stained the hemi-diaphragm. IgG anti-GM1 mAb binds to the presynaptic nerve terminal of neuromuscular junctions. Therefore, we suggest that the inhibitory effect of IgG anti-GM1 mAb on spontaneous muscle action potentials is related to the GM1 epitope in presynaptic motor nerve terminals at the NMJs.
authors.affiliation: Department of Medicinal Pharmacology, Showa Pharmaceutical University, Higashitamagawagakuen, Machida, Tokyo, 194-8543, Japan.
authors.forename: Sayako
authors.initials: S
authors.lastname: Hotta
authors.forename: Takumi
authors.initials: T
authors.lastname: Nagaoka
authors.forename: Kyoji
authors.initials: K
authors.lastname: Taguchi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Iku
authors.initials: I
authors.lastname: Utsnomiya
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Masuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yuki
mesh_terms: D000200:Action Potentials; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D005677:G(M1) Ganglioside / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D066298:In Vitro Techniques; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000502:physiology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000502:physiology; D050765:Qa-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D009418:S100 Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D016900:Neurofilament Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D050765:Qa-SNARE Proteins; D009418:S100 Proteins; C051774:neurofilament protein H; D005677:G(M1) Ganglioside; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase; D017364:Collagenases